RESUMO
Activation of Wingless (Wnt)/beta-catenin signaling is a hallmark of colorectal carcinoma (CRC). It is very important to find out the molecular mechanism for the hyperactivation of Wnt/beta-catenin signaling and identify novel therapeutic targets. Kindlin-2, a regulator of integrins, recently has been found to be involved in the tumorigenesis. However, its expression profile and functions in the progression of CRC remain poorly understood. Here, we found that the expression of Kindlin-2 was downregulated in the CRC tissues. Moreover, overexpression of Kindlin-2 in CRC cells and normal colon epithelial cells inhibited cell proliferation and migration, while downregulation of Kindlin-2 promoted the tumorigenecity of CRC cells in vitro and in vivo. Mechanistically, Kindlin-2 decreased the phosphorylation of Ser9 in glycogen synthase kinase (GSK) 3beta and promoted the ubiquitination of beta-catenin. Taken together, our study suggests the suppressive roles of Kindlin-2 in the pathogenesis of CRC.
Assuntos
Carcinogênese/genética , Proliferação de Células/genética , Neoplasias Colorretais/genética , Proteínas de Membrana/genética , Proteínas de Neoplasias/genética , Animais , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Quinase 3 da Glicogênio Sintase/genética , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Células HCT116 , Humanos , Proteínas de Membrana/biossíntese , Camundongos , Proteínas de Neoplasias/biossíntese , Via de Sinalização Wnt , beta Catenina/genéticaRESUMO
Effect of erlotinib combined with cisplatin on tumor growth, interleukin-6 (IL-6) and interleukin-12 (IL-12) in mice with Lewis lung cancer (LLC) was investigated. Forty-four pure inbred SPF C57BL/6J mice were modeled for LLC and randomized into groups A, B, C and D (n=11 each group). Mice in group A were given normal saline, group B was given erlotinib, group C was given cisplatin injection and group D erlotinib combined with cisplatin. Tumor growth of the mice was observed and the tumor mass was measured. Serum IL-6 and IL-12 levels were measured by enzyme-linked immunosorbent assay (ELISA) 40 days later. At different time-points after medication, tumor volume in group D was significantly lower than that in groups A, B and C (P<0.05), and that in groups B and C was significantly lower than that in group A (P<0.05), whereas there was no significant difference between groups B and C (P>0.05). Tumor mass in groups B, C and D was significantly lower than that in group A (P<0.05), and that in group D was significantly lower than that in groups B and C (P<0.05), whereas there was no significant difference between groups B and C (P>0.05). Compared with groups B and C, mice in group D had significantly lower IL-6 level (P<0.05), but significantly higher IL-12 level (P<0.05). There was no significant difference in IL-6 and IL-12 levels between groups B and C (P>0.05). In conclusion, erlotinib combined with cisplatin can inhibit the tumor growth of mice with LLC, and inhibition of IL-6 level and upregulation of IL-12 level may be one of its therapeutic mechanisms.